Sex differences in morning cortisol in youth at ultra-high-risk for psychosis

Abstract

Summary Research suggests abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function play an important role in the pathophysiology of psychosis. However, there is limited research on the biological stress system in young people at ultra high risk (UHR) for psychosis. Morning cortisol levels are particularly relevant to study in this context, as these markers reflect HPA regulation. This is the first examination of sex differences in morning cortisol levels in UHR individuals. Twenty-eight UHR and 22 matched healthy control participants were assessed in respect to symptoms and had home-based collection of salivary cortisol over three time points in the morning. It was predicted that the UHR participants would exhibit lower morning cortisol levels and lower cortisol would be associated with greater symptomatology (i.e. higher positive, negative, and depressive symptoms). Additionally, sex differences in morning cortisol levels were explored based on recent evidence suggesting that sex differences may play an important role in the exacerbation of psychosis. While there were no group differences in morning salivary cortisol secretion, there was a sex by time interaction among UHR individuals, such that only UHR males exhibited flat cortisol levels across two hours after awakening, whereas UHR females had a pattern of cortisol secretion similar to healthy controls, even among medication-free individuals (F = 6.34, p = 0.004). Cortisol AUC (area under the curve) across the three time points had a trend association (medium effect size; r = 0.34, p = 0.08) with depressive, but not positive or negative, symptom severity. These results stress the importance of considering sex differences in the psychosis-risk period, as they improve understanding of pathogenic processes.

Role of Cortisol and Testosterone in Risky Decision-Making: Deciphering Male Decision-Making in the Iowa Gambling Task

“…The results confirmed cortisol decline in the all-male sample of the present study. Blunted cortisol decline in healthy participants is characteristic of early life stressors ( Kuras et al, 2017 ) and is considered particularly maladaptive in males ( Carol et al, 2016 ). Furthermore, the results indicated that cortisol decline was independent of counting type.…”

The relationship between cannabis use and cortisol levels in youth at ultra high-risk for psychosis

“…A better understanding of how cannabis use may be related to HPA dysfunction in UHR individuals could clarify inconsistencies as UHR individuals use cannabis at higher rates and frequency (Addington et al, 2014; Ksir and Hart, 2016), and the current results indicate that UHR individuals who use cannabis have higher cortisol levels. Future studies should also examine how cannabis use relates to other aspects of HPA axis function, as patients with schizophrenia experienced a flattened cortisol awakening response after cannabis exposure (Monteleone et al, 2014) and UHR individuals show blunted CAR and morning cortisol levels during the first hour after awakening in a home setting (Carol et al, 2016; Day et al, 2014). …”

“…Although our sample size is comparable to other studies conducted in the UHR population (Corcoran et al, 2012; Pruessner et al, 2013) and we controlled for age in our analysis, future studies with larger samples, and more power to control for multiple comparisons, should be conducted before any definitive conclusions are made. Larger studies should also examine sex-differences in cannabis use and cortisol levels as sex-differences in morning cortisol samples collected in home samples in UHR youth and in patients with schizophrenia have been reported (Carol et al, 2016; Pruessner et al, 2008). Additionally, while the current methods used to collect and analyze cortisol levels are consistent with previous examinations (Mittal and Walker, 2011; Walker et al, 2013), future studies that collect more cortisol samples across the day, especially the cortisol awakening response (CAR), and over consecutive days are needed to better understand cannabis use and the 24-hour circadian cycle of the HPA axis in UHR youth.…”

“…The protocol and informed consent procedures were approved by the Institutional Review Board. The authors would also like to note that 31 out of the 75 participants included in the present study participated in a previous study at the ADAPT research program (Carol et al, 2016). …”

Stress, Cortisol and NR3C1 in At-Risk Individuals for Psychosis: A Mendelian Randomization Study

“…Cortisol awakening response could be significantly lower in males with FEP compared to male controls and affected females ( 11 ). Sex differences have also been suggested in morning cortisol levels in the at-risk stage ( 12 ). This moderating effect of sex might further be seen at the molecular level, on the glucocorticoid nuclear receptor NR3C1 , which acts as a transcription factor that binds to glucocorticoid response elements and regulates gene expression upon stress.…”